RNase H active site inhibitors of human immunodeficiency virus type 1 reverse transcriptase: design, biochemical activity, and structural information.

No abstract is available for this paper.

• Publication year

  2009

• Venue

  Journal of Medicinal Chemistry

• Publication date

  2009-09-10

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1021/jm900597qPMID 19791799
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Derivatives of 5-nitro-furan-2-carboxylic acid carbamoylmethyl ester inhibit RNase H activity associated with HIV-1 reverse transcriptase.

  2009cited by this paper
• HIV-1 reverse transcriptase can simultaneously engage its DNA/RNA substrate at both DNA polymerase and RNase H active sites: implications for RNase H inhibition.

  2009cited by this paper
• An equivalent metal ion in one- and two-metal-ion catalysis

  2008cited by this paper
• Design, synthesis, and biological evaluation of a series of 2-hydroxyisoquinoline-1,3(2H,4H)-diones as dual inhibitors of human immunodeficiency virus type 1 integrase and the reverse transcriptase RNase H domain.

  2008cited by this paper
• Metal chelators as antiviral agents.

  2007cited by this paper
• Substrate-dependent inhibition or stimulation of HIV RNase H activity by non-nucleoside reverse transcriptase inhibitors (NNRTIs).

  2007cited by this paper
• Dihydroxypyrimidine-4-carboxamides as novel potent and selective HIV integrase inhibitors.

  2007cited by this paper
• HIV drug development: the next 25 years

  2007cited by this paper
• 2-(2-Thienyl)-5,6-dihydroxy-4-carboxypyrimidines as inhibitors of the hepatitis C virus NS5B polymerase: discovery, SAR, modeling, and mutagenesis.

  2006cited by this paper
• 4,5-dihydroxypyrimidine carboxamides and N-alkyl-5-hydroxypyrimidinone carboxamides are potent, selective HIV integrase inhibitors with good pharmacokinetic profiles in preclinical species.

  2006cited by this paper
• Recent progress in the design of small molecule inhibitors of HIV RNase H.

  2006cited by this paper
• Inhibition of Human Immunodeficiency Virus Type 1 Reverse Transcriptase, RNase H, and Integrase Activities by Hydroxytropolones

  2005cited by this paper
• Dissecting the effects of DNA polymerase and ribonuclease H inhibitor combinations on HIV-1 reverse-transcriptase activities.

  2005cited by this paper
• Selective inhibition of HIV-1 reverse transcriptase-associated ribonuclease H activity by hydroxylated tropolones

  2005cited by this paper
• The identification and optimization of a N-hydroxy urea series of flap endonuclease 1 inhibitors.

  2005cited by this paper
• Crystal structures of RNase H bound to an RNA/DNA hybrid: substrate specificity and metal-dependent catalysis.

  2005cited by this paper
• Activity of the isolated HIV RNase H domain and specific inhibition by N-hydroxyimides.

  2004cited by this paper
• Enzymatic synthesis of tea theaflavin derivatives and their anti-inflammatory and cytotoxic activities.

  2004cited by this paper
• HCV NS5b RNA-dependent RNA polymerase inhibitors: from alpha,gamma-diketoacids to 4,5-dihydroxypyrimidine- or 3-methyl-5-hydroxypyrimidinonecarboxylic acids. Design and synthesis.

  2004cited by this paper
• A fluorescence-based high-throughput screening assay for inhibitors of human immunodeficiency virus-1 reverse transcriptase-associated ribonuclease H activity.

  2003cited by this paper
• Design and synthesis of 8-hydroxy-[1,6]naphthyridines as novel inhibitors of HIV-1 integrase in vitro and in infected cells.

  2003cited by this paper
• Use of a pharmacophore model to discover a new class of influenza endonuclease inhibitors.

  2003cited by this paper
• Two-metal ion mechanism of RNA cleavage by HIV RNase H and mechanism-based design of selective HIV RNase H inhibitors.

  2003cited by this paper
• Metal-ion stoichiometry of the HIV-1 RT ribonuclease H domain: evidence for two mutually exclusive sites leads to new mechanistic insights on metal-mediated hydrolysis in nucleic acid biochemistry

  2000cited by this paper
• Manganese as a Replacement for Magnesium and Zinc: Functional Comparison of the Divalent Ions

  1999cited by this paper
• α-Hydroxytropolones: A New Class of Potent Inhibitors of Inositol Monophosphatase and Other Bimetallic Enzymes

  1997cited by this paper
• 6 Roles of Ribonuclease H in Reverse Transcription

  1993cited by this paper
• Abortive reverse transcription by mutants of Moloney murine leukemia virus deficient in the reverse transcriptase-associated RNase H function

  1991cited by this paper
• Crystal structure of the ribonuclease H domain of HIV-1 reverse transcriptase.

  1991cited by this paper
• Illimaquinone, a selective inhibitor of the RNase H activity of human immunodeficiency virus type 1 reverse transcriptase

  1990cited by this paper

• Screening for Potential Antiviral Compounds from Cyanobacterial Secondary Metabolites Using Machine Learning

  2024cites this paper
• Inhibiting HCMV pUL89-C Endonuclease with Metal-Binding Compounds.

  2023cites this paper
• Sticklac-Derived Natural Compounds Inhibiting RNase H Activity of HIV-1 Reverse Transcriptase.

  2023cites this paper
• Targeting Metalloenzymes: The “Achilles’ Heel” of Viruses and Parasites

  2023cites this paper
• Targeting Ribonucleases with Small Molecules and Bifunctional Molecules

  2023cites this paper
• Predicted structure of the hepatitis B virus polymerase reveals an ancient conserved protein fold

  2022cites this paper
• Computational and Crystallographic Analysis of Binding Structures of Inhibitory Compounds for HIV-1 RNase H Activity

  2022cites this paper
• Design, synthesis, and biological evaluation of novel double-winged galloyl derivatives as HIV-1 RNase H inhibitors.

  2022cites this paper
• Chalcogenium-AZT derivatives: a plausible strategy to tackle the RT-inhibitors-related oxidative stress while maintaining their anti-HIV properties.

  2022cites this paper
• 4,5-Dihydroxypyrimidine Methyl Carboxylates, Carboxylic Acids, and Carboxamides as Inhibitors of Human Cytomegalovirus pUL89 Endonuclease.

  2022cites this paper
• Discovery of Novel 3-Hydroxyquinazoline-2,4(1H,3H)-Dione Derivatives: A Series of Metal Ion Chelators with Potent Anti-HCV Activities

  2022cites this paper
• Metal binding 6-arylthio-3-hydroxypyrimidine-2,4-diones inhibited human cytomegalovirus by targeting the pUL89 endonuclease of the terminase complex.

  2021cites this paper
• Retroviral RNase H: Structure, mechanism, and inhibition.

  2021cites this paper
• HIV-1 Reverse Transcriptase/Integrase Dual Inhibitors: A Review of Recent Advances and Structure-activity Relationship Studies

  2021cites this paper
• Large Multidomain Protein NMR: HIV-1 Reverse Transcriptase Precursor in Solution

  2020cites this paper
• Allostery as Structure‐Encoded Collective Dynamics

  2020cites this paper
• Cations in motion: QM/MM studies of the dynamic and electrostatic roles of H+ and Mg2+ ions in enzyme reactions.

  2020cites this paper
• Design, synthesis and biological evaluation of 3-hydroxyquinazoline-2,4(1H,3H)-diones as dual inhibitors of HIV-1 reverse transcriptase-associated RNase H and integrase.

  2019cites this paper
• HIV-1 Reverse Transcriptase: A Metamorphic Protein with Three Stable States.

  2019influential citation
• Pharmacophore-based design of novel 3-hydroxypyrimidine-2,4-dione subtypes as inhibitors of HIV reverse transcriptase-associated RNase H: Tolerance of a nonflexible linker.

  2019cites this paper
• Cutting into the Substrate Dominance: Pharmacophore and Structure-Based Approaches toward Inhibiting Human Immunodeficiency Virus Reverse Transcriptase-Associated Ribonuclease H.

  2019cites this paper
• Design, Synthesis and Biological Evaluation of Some New Derivatives of Azoles Bearing Pyrrolo [2, 3-d] Pyrimidine Nucleus as Janus Tyrosine Kinase Inhibitors for the Treatment of Auto Immune Disease

  2019cites this paper
• In silico study of 3-hydroxypyrimidine-2,4-diones as inhibitors of HIV RT-associated RNase H using molecular docking, molecular dynamics, 3D-QSAR, and pharmacophore models

  2019cites this paper
• Determinants of Active-Site Inhibitor Interaction with HIV-1 RNase H.

  2019cites this paper
• Ribonuclease H, an unexploited target for antiviral intervention against HIV and hepatitis B virus.

  2019cites this paper
• Targeting Metalloenzymes for Therapeutic Intervention.

  2018cites this paper
• 6-Arylthio-3-hydroxypyrimidine-2,4-diones potently inhibited HIV reverse transcriptase-associated RNase H with antiviral activity.

  2018cites this paper
• Developing and Evaluating Inhibitors against the RNase H Active Site of HIV-1 Reverse Transcriptase

  2018cites this paper
• 6-Biphenylmethyl-3-hydroxypyrimidine-2,4-diones potently and selectively inhibited HIV reverse transcriptase-associated RNase H.

  2018cites this paper
• Structure-guided approach identifies a novel class of HIV-1 ribonuclease H inhibitors: binding mode insights through magnesium complexation and site-directed mutagenesis studies.

  2018cites this paper
• Pharmacophore requirements for HIV-1 reverse transcriptase inhibitors that selectively "Freeze" the pre-translocated complex during the polymerization catalytic cycle.

  2018cites this paper
• A review on architecture of the gag-pol ribosomal frameshifting RNA in human immunodeficiency virus: a variability survey of virus genotypes

  2017cites this paper
• Inhibition of hepatitis B virus replication by N‐hydroxyisoquinolinediones and related polyoxygenated heterocycles

  2017cites this paper
• Inhibitors of Influenza Virus Polymerase Acidic (PA) Endonuclease: Contemporary Developments and Perspectives.

  2017cites this paper
• Evaluation of Broad Anti-Herpesviral Activity with a-Hydroxytropolones

  2017cites this paper
• Design, synthesis and biological evaluations of N-Hydroxy thienopyrimidine-2,4-diones as inhibitors of HIV reverse transcriptase-associated RNase H.

  2017cites this paper
• Identification of spirocyclic or phosphate substituted quinolizine derivatives as novel HIV-1 integrase inhibitors: a patent evaluation of WO2016094197A1, WO2016094198A1 and WO2016154527A1

  2017cites this paper
• Viral reverse transcriptases.

  2017cites this paper
• Synthetic α-Hydroxytropolones as Inhibitors of HIV Reverse Transcriptase Ribonuclease H Activity.

  2016cites this paper
• 3-Hydroxypyrimidine-2,4-diones as Selective Active Site Inhibitors of HIV Reverse Transcriptase-Associated RNase H: Design, Synthesis, and Biochemical Evaluations.

  2016cites this paper
• The Chemistry and Bio-Medicinal Significance of Pyrimidines & Condensed Pyrimidines.

  2016cites this paper
• Unfolding the HIV-1 reverse transcriptase RNase H domain – how to lose a molecular tug-of-war

  2016cites this paper
• Design, Synthesis, and Biological Evaluations of Hydroxypyridonecarboxylic Acids as Inhibitors of HIV Reverse Transcriptase Associated RNase H.

  2016cites this paper
• Functionally Relevant Specific Packing Can Determine Protein Folding Routes.

  2016cites this paper
• Fragment Based Strategies for Discovery of Novel HIV-1 Reverse Transcriptase and Integrase Inhibitors.

  2015cites this paper
• The hepatitis B virus ribonuclease H as a drug target.

  2015cites this paper
• Studies Toward a General Synthesis of Poly- Substituted Alpha-Hydroxytropolones

  2015cites this paper
• Docking studies of some 5-hydroxypyridine-4-one derivatives: evaluation of integrase and ribonuclease H domain of reverse transcriptase as possible targets for anti-HIV-1 activity

  2015influential citation
• Studies Toward a General Synthesis of Poly-Substituted Alpha-Hydroxytropolones

  2015cites this paper
• Metalloprotein Inhibitors for the Treatment of Human Diseases.

  2015cites this paper
• (3Z)-3-(2-[4-(aryl)-1,3-thiazol-2-yl]hydrazin-1-ylidene)-2,3-dihydro-1H-indol-2-one derivatives as dual inhibitors of HIV-1 reverse transcriptase.

  2015cites this paper
• Structure of a dihydroxycoumarin active-site inhibitor in complex with the RNase H domain of HIV-1 reverse transcriptase and structure-activity analysis of inhibitor analogs.

  2014cites this paper
• Design, Synthesis, and Biological Evaluation of 1,3‐Diarylpropenones as Dual Inhibitors of HIV‐1 Reverse Transcriptase

  2014cites this paper
• Past and Future. Current Drugs Targeting HIV-1 Integrase and Reverse Transcriptase-Associated Ribonuclease H Activity: Single and Dual Active Site Inhibitors

  2014cites this paper
• "Old Dogs with New Tricks": exploiting alternative mechanisms of action and new drug design strategies for clinically validated HIV targets.

  2014cites this paper
• Recent progress in the research of small molecule HIV-1 RNase H inhibitors.

  2014cites this paper
• Inhibition of Foamy Virus Reverse Transcriptase by Human Immunodeficiency Virus Type 1 RNase H Inhibitors

  2014cites this paper
• Inhibition of the Ribonuclease H Activity of HIV-1 Reverse Transcriptase by GSK5750 Correlates with Slow Enzyme-Inhibitor Dissociation*

  2014cites this paper
• Pyridopyrimidinone inhibitors of HIV-1 RNase H.

  2014cites this paper
• The biology and synthesis of α-hydroxytropolones.

  2014cites this paper
• "Old friends in new guise": exploiting privileged structures for scaffold re-evolution/refining.

  2014cites this paper
• Identification of Highly Conserved Residues Involved in Inhibition of HIV-1 RNase H Function by Diketo Acid Derivatives

  2014cites this paper
• Hydroxylated Tropolones Inhibit Hepatitis B Virus Replication by Blocking Viral Ribonuclease H Activity

  2014cites this paper
• Characterization of the mechanism of action of new HIV-1 reverse transcriptase-associated ribonuclease H inhibitors

  2014cites this paper
• Can the ever-promising target HIV reverse transcriptase-associated RNase H become a success story for drug development?

  2014cites this paper
• Inhibitors of Nucleotidyltransferase Superfamily Enzymes Suppress Herpes Simplex Virus Replication

  2014cites this paper
• Simplex Virus Replication Superfamily Enzymes Suppress Herpes Inhibitors of Nucleotidyltransferase

  2014cites this paper
• Virtual Screening Models for Prediction of HIV-1 RT Associated RNase H Inhibition

  2013cites this paper
• Real time monitoring of junction ribonuclease activity of RNase H using chimeric molecular beacons.

  2013cites this paper
• The Hepatitis B Virus Ribonuclease H Is Sensitive to Inhibitors of the Human Immunodeficiency Virus Ribonuclease H and Integrase Enzymes

  2013influential citation
• Ribonuclease H Inhibitors: Structural and Molecular Biology

  2013cites this paper
• Active site and allosteric inhibitors of the ribonuclease H activity of HIV reverse transcriptase.

  2013cites this paper
• Molecular aspects of the RT/drug interactions. Perspective of dual inhibitors.

  2013cites this paper
• Viral enzymes containing magnesium: Metal binding as a successful strategy in drug design

  2012cites this paper
• Targeting the retroviral ribonuclease H by rational drug design.

  2012cites this paper
• Identification of HIV-1 reverse transcriptase dual inhibitors by a combined shape-, 2D-fingerprint- and pharmacophore-based virtual screening approach.

  2012cites this paper
• Theoretical studies of HIV-1 reverse transcriptase inhibition.

  2012cites this paper
• Development of a series of 3-hydroxyquinolin-2(1H)-ones as selective inhibitors of HIV-1 reverse transcriptase associated RNase H activity.

  2012cites this paper
• The design, synthesis and biological evaluations of C-6 or C-7 substituted 2-hydroxyisoquinoline-1,3-diones as inhibitors of hepatitis C virus.

  2012cites this paper
• Structural and Inhibition Studies of the RNase H Function of Xenotropic Murine Leukemia Virus-Related Virus Reverse Transcriptase

  2012cites this paper
• Structural modulation study of inhibitory compounds for ribonuclease H activity of human immunodeficiency virus type 1 reverse transcriptase.

  2012cites this paper
• Structural Basis of the Allosteric Inhibitor Interaction on the HIV‐1 Reverse Transcriptase RNase H Domain

  2012cites this paper
• Metal and ligand binding to the HIV-RNase H active site are remotely monitored by Ile556

  2012cites this paper
• Structural and Biochemical Basis for Development of Influenza Virus Inhibitors Targeting the PA Endonuclease

  2012cites this paper
• Gold compounds with anti-HIV and immunomodulatory activity

  2012cites this paper
• Inhibitors of HIV-1 Reverse Transcriptase—Associated Ribonuclease H Activity

  2012influential citation
• Evaluation of Different Mycobacterial Species for Drug Discovery and Characterisation of Novel Inhibitors of Mycobacterium Tuberculosis

  2012cites this paper
• Identification of Alternative Binding Sites for Inhibitors of HIV-1 Ribonuclease H Through Comparative Analysis of Virtual Enrichment Studies

  2011cites this paper
• Structural and biochemical study on the inhibitory activity of derivatives of 5-nitro-furan-2-carboxylic acid for RNase H function of HIV-1 reverse transcriptase.

  2011cites this paper
• Interaction of HIV‐1 Reverse Transcriptase Ribonuclease H with an Acylhydrazone Inhibitor

  2011cites this paper
• Synopsis of some recent tactical application of bioisosteres in drug design.

  2011cites this paper
• Expression of an Mg2+-Dependent HIV-1 RNase H Construct for Drug Screening

  2011cites this paper
• Mutagenesis of Human Immunodeficiency Virus Reverse Transcriptase p51 Subunit Defines Residues Contributing to Vinylogous Urea Inhibition of Ribonuclease H Activity*

  2011cites this paper
• Synthesis, activity, and structural analysis of novel α-hydroxytropolone inhibitors of human immunodeficiency virus reverse transcriptase-associated ribonuclease H.

  2011cites this paper
• HIV-1 reverse transcriptase inhibitors: beyond classic nucleosides and non-nucleosides

  2011cites this paper
• Fluoren-9-ylidene Hydrazine Inhibitors of HIV-1 Ribonuclease H

  2011influential citation
• Structural and Binding Analysis of Pyrimidinol Carboxylic Acid and N-Hydroxy Quinazolinedione HIV-1 RNase H Inhibitors

  2011influential citation
• HIV-1 Ribonuclease H: Structure, Catalytic Mechanism and Inhibitors

  2010influential citation
• Small molecule inhibitors of HIV RT Ribonuclease H.

  2010cites this paper
• Potent and selective HIV-1 ribonuclease H inhibitors based on a 1-hydroxy-1,8-naphthyridin-2(1H)-one scaffold.

  2010cites this paper